不同剂量舒芬太尼预处理对大鼠的延迟性心肌保护作用

Delayed cardioprotection of different doses of sufentanil preconditioning in rats

目的评价不同剂量舒芬太尼预处理的延迟性心肌保护作用。方法成年雄性Wistar大鼠42只，体重250—300g，随机分为7组（n=6），心肌缺血前24h，Ⅰ组腹腔注射生理盐水1ml／kg，Ⅱ组、Ⅲ组、Ⅳ组和Ⅴ组分别腹腔注射舒芬太尼1、5、10、20μg／kg，Ⅵ组和Ⅶ组分别接受与Ⅴ组、Ⅰ组相同的处理，注射舒芬太尼前15min均腹腔注射非选择性阿片受体阻断剂纳洛酮1mg／kg。采用结扎冠状动脉左前降支的方法建立心肌缺血再灌注模型，缺血45min，再灌注120min。于缺血前、缺血期每隔15min、再灌注期每隔15min监测心率（HR）和平均动脉压（MAP），计算HR与MAP的乘积（RPP）；于缺血前即刻、缺血45min和再灌注120min时抽取右颈内动脉血样，测定血清肌酸激酶同工酶（CK-MB）活性；再灌注120min时取心脏，测定左心室面积（LVA）、心肌梗塞区面积（IA）及缺血危险区面积（AAR），计算AAR／LVA和IA／AAR。结果与Ⅰ组比较，Ⅲ组再灌注120min、Ⅳ组和Ⅴ组缺血45min和再灌注120min时血清CK-MB活性降低，Ⅲ组、Ⅳ组和Ⅴ组IA／AAR降低（P〈0．05）；与Ⅱ组比较，Ⅲ组、Ⅳ组和Ⅴ组缺血45min和再灌注120min时血清CK-MB活性及IA／AAR均降低（P〈0．05）；与Ⅲ组比较，Ⅳ组和Ⅴ组缺血45min和再灌注120min时血清CK-MB活性及IA／AAR均降低（P〈0．05）；与Ⅴ组比较，Ⅵ组缺血45min和再灌注120min时血清CK-MB活性及IA／AAR均升高（P〈0．05）；各组AAR，LVA差异无统计学意义（P〉0．05）。结论舒芬太尼预处理可通过激活阿片受体对缺血再灌注心肌产生延迟性保护作用，呈剂量依赖性，但具有封顶效应。

Objective To investigate the delayed cadioprotection of different doses of sufentanil preconditioning and its dose-dependent relation. Methods Forty-two adult male Wistar rats, weighing 250-300 g, were randomly divided into 7 groups （ n = 6 each） . Twenty-four hours before myocardial isehemia, in group Ⅰ , rats were treated with intraperitoneal （IP） normal saline 1 ml/kg;in group Ⅱ , Ⅲ , Ⅳ and Ⅴ , rats were treated with 4 different doses of IP sufentanil 1, 5, 10 and 20 μg/kg respectively ; in group Ⅵ and Ⅶ , rats were treated according to the same experimental protocols as those in group Ⅴ and Ⅰ respectively in addition to receiving nonselective opioid receptor antagonist naloxone 1 mg/kg or normal saline. Myocardial ischemia was induced by IP 15 min before preconditioning with sufentanil 20 μg/kg occlusion of left anterior descending coronary artery for 45 min followed by 120 min reperfusion. HR and MAP were recorded before ischemia and every 15 min during myocardial ischemia and reperfusion period. The rate-pressure product（ RPP）was calculated. The blood samples from right internal carotid artery were obtained for determination of serum activity of CK-MB immediately before ischemia, and at 45 min of ischemia and 120 min of reperfusion. Hearts were removed to measure the left ventricle area （LVA） the myocardial infarct area （IA） and the area at risk （AAR） at 120 min of reperfusion and AAR/LVA and IA/AAR were calculated. Results There were no significant differences in HR, MAP and RPP at every measurement point during the experiment among all groups. As compared to group Ⅰ , serum CK-MB activity was significantly decreased in group Ⅲ at 120 min of reperfusion and in group Ⅳ and Ⅴ at 45 min of ischemia and 120 min of reperfusion, and IA/AAR was decreased in group Ⅲ, Ⅳ and Ⅴ . The serum CK-MB activity at 45 min of ischemia and 120 min of reperfusion and IA/AAR were significantly lower in group Ⅲ , Ⅳ and Ⅴ than in group Ⅱ , and in group Ⅳ and Ⅴ than in group Ⅲ . The serum activity of CK-MB at 45 min of ischemia and 120 min of reperfusion and IA/AAR were significantly higher in group Ⅵ than in group Ⅴ. There was no significant difference in AAR/LVA among all groups. Conclusion Sufentanil preconditioning can produce delayed cardioprotection through activating opioid receptors in a dose-dependent manner, but there is ceiling effect.